Risk Stratification Model for Resected Squamous-Cell Lung Cancer Patients According to Clinical and Pathological Factors

Introduction: The aim of this analysis (AIRC-MFAG project no. 14282) was to define a risk classification for resected squamous-cell lung cancer based on the combination of clinicopathological predictors to provide a practical tool to evaluate patients’ prognosis. Methods: Clinicopathological data were retrospectively correlated to disease-free/cancer-specific/overall survival (DFS/CSS/OS) using a Cox model. Individual patient probability was estimated by logistic equation. A continuous score to identify risk classes was derived according to model ratios and dichotomized according to prognosis with receiver operating characteristic analysis. Results: Data from 573 patients from five institutions were gathered. Four hundred ninety-four patients were evaluable for clinical analysis (median age: 68 years; male/female: 403/91; T-descriptor according to TNM 7th edition 1–2/3–4: 330/164; nodes 0/>0: 339/155; stages I and II/III and IV: 357/137). At multivariate analysis, age, T-descriptor according to TNM 7th edition, nodes, and grading were independent predictors for DFS and OS; the same factors, except age and grading, predicted CSS. Multivariate model predict individual patient probability with high prognostic accuracy (0.67 for DFS). On the basis of receiver operating characteristic-derived cutoff, a two-class model significantly differentiated low-risk and high-risk patients for 3-year DFS (64.6% and 32.4%, p < 0.0001), CSS (84.4% and 44.5%, p < 0.0001), and OS (77.3% and 38.8%, p < 0.0001). A three-class model separated low-risk, intermediate-risk, and high-risk patients for 3-year DFS (64.6%, 39.8%, and 21.8%, p < 0.0001), CSS (84.4%, 55.4%, and 30.9%, p< 0.0001), and OS (77.3%, 47.9%, and 27.2%, p < 0.0001). Conclusions: A risk stratification model including often adopted clinicopathological parameters accurately separates resected squamous-cell lung cancer patients into different risk classes. The project is currently ongoing to integrate the clinicopathological model with investigational molecular predictors.

[1]  Li Zhang,et al.  Development and validation of a nomogram for predicting survival in patients with resected non-small-cell lung cancer. , 2015, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[2]  Y. Takeshima,et al.  Prognostic impact of lymphatic invasion for pathological stage I squamous cell carcinoma of the lung , 2015, General Thoracic and Cardiovascular Surgery.

[3]  M. Kohno,et al.  Prognostic Factors Based on Clinicopathological Data Among the Patients with Resected Peripheral Squamous Cell Carcinomas of the Lung , 2014, Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer.

[4]  C. Sima,et al.  Comprehensive Pathological Analyses in Lung Squamous Cell Carcinoma: Single Cell Invasion, Nuclear Diameter, and Tumor Budding Are Independent Prognostic Factors for Worse Outcomes , 2014, Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer.

[5]  R. Osarogiagbon,et al.  Number of lymph nodes associated with maximal reduction of long-term mortality risk in pathologic node-negative non-small cell lung cancer. , 2014, The Annals of thoracic surgery.

[6]  Michael Thomas,et al.  Crizotinib versus chemotherapy in advanced ALK-positive lung cancer. , 2013, The New England journal of medicine.

[7]  Akiko Miyagi Maeshima,et al.  Interobserver Agreement in the Nuclear Grading of Primary Pulmonary Adenocarcinoma , 2013, Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer.

[8]  A. Yoshizawa,et al.  Validation of the IASLC/ATS/ERS Lung Adenocarcinoma Classification for Prognosis and Association with EGFR and KRAS Gene Mutations: Analysis of 440 Japanese Patients , 2013, Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer.

[9]  S. Beghelli,et al.  A clinical-biological risk stratification model for resected gastric cancer: prognostic impact of Her2, Fhit, and APC expression status. , 2012, Annals of oncology : official journal of the European Society for Medical Oncology.

[10]  Steven J. M. Jones,et al.  Comprehensive genomic characterization of squamous cell lung cancers , 2012, Nature.

[11]  H. Kijima,et al.  Tumor budding is a significant indicator of a poor prognosis in lung squamous cell carcinoma patients , 2012, Molecular medicine reports.

[12]  Michael Thomas,et al.  The novel histologic International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society classification system of lung adenocarcinoma is a stage-independent predictor of survival. , 2012, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[13]  Iver Petersen,et al.  Interobserver variability in the application of the novel IASLC/ATS/ERS classification for pulmonary adenocarcinomas , 2012, European Respiratory Journal.

[14]  E. Felip,et al.  Erlotinib versus standard chemotherapy as first-line treatment for European patients with advanced EGFR mutation-positive non-small-cell lung cancer (EURTAC): a multicentre, open-label, randomised phase 3 trial. , 2012, The Lancet. Oncology.

[15]  J. Usuda,et al.  Prognostic Impact of Number of Resected and Involved Lymph Nodes at Complete Resection on Survival in Non-small Cell Lung Cancer , 2011, Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer.

[16]  A. Yılmaz,et al.  Clinical impact of visceral pleural, lymphovascular and perineural invasion in completely resected non-small cell lung cancer. , 2011, European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery.

[17]  Shun‐ichi Watanabe,et al.  Which is the Better Prognostic Factor for Resected Non-small Cell Lung Cancer: The Number of Metastatic Lymph Nodes or the Currently Used Nodal Stage Classification? , 2011, Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer.

[18]  A. Gemma,et al.  F1000 highlights , 2010 .

[19]  R. Welsh,et al.  Age, tumor size, type of surgery, and gender predict survival in early stage (stage I and II) non-small cell lung cancer after surgical resection. , 2010, Lung cancer.

[20]  C. Gridelli,et al.  Clinical assessment of patients with advanced non-small-cell lung cancer eligible for second-line chemotherapy: a prognostic score from individual data of nine randomised trials. , 2010, European journal of cancer.

[21]  S. Toyooka,et al.  Gefitinib versus cisplatin plus docetaxel in patients with non-small-cell lung cancer harbouring mutations of the epidermal growth factor receptor (WJTOG3405): an open label, randomised phase 3 trial. , 2010, The Lancet. Oncology.

[22]  A. Marchetti,et al.  A novel clinical prognostic score incorporating the number of resected lymph-nodes to predict recurrence and survival in non-small-cell lung cancer. , 2009, Lung cancer.

[23]  Soonmyung Paik,et al.  Use of archived specimens in evaluation of prognostic and predictive biomarkers. , 2009, Journal of the National Cancer Institute.

[24]  John J. Crowley,et al.  国际肺癌研究会分期项目——采用外科治疗的非小细胞肺癌的预后因素和病理TNM分期 , 2010, Zhongguo fei ai za zhi = Chinese journal of lung cancer.

[25]  J. Crowley,et al.  The Impact of Additional Prognostic Factors on Survival and their Relationship with the Anatomical Extent of Disease Expressed by the 6th Edition of the TNM Classification of Malignant Tumors and the Proposals for the 7th Edition , 2008, Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer.

[26]  G. Raj,et al.  How to build and interpret a nomogram for cancer prognosis. , 2008, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[27]  J. Crowley,et al.  The IASLC Lung Cancer Staging Project: Proposals for the Revision of the TNM Stage Groupings in the Forthcoming (Seventh) Edition of the TNM Classification of Malignant Tumours , 2007, Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer.

[28]  G. Giaccone,et al.  Is a patient's self-reported health-related quality of life a prognostic factor for survival in non-small-cell lung cancer patients? A multivariate analysis of prognostic factors of EORTC study 08975. , 2006, Annals of oncology : official journal of the European Society for Medical Oncology.

[29]  T. Alonzo Standards for reporting prognostic tumor marker studies. , 2005, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[30]  E. Miyaoka,et al.  Prognosis of 6644 resected non-small cell lung cancers in Japan: a Japanese lung cancer registry study. , 2005, Lung cancer.

[31]  M. Pencina,et al.  Overall C as a measure of discrimination in survival analysis: model specific population value and confidence interval estimation , 2004, Statistics in medicine.

[32]  A. Gajra,et al.  Effect of number of lymph nodes sampled on outcome in patients with stage I non-small-cell lung cancer. , 2003, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[33]  M. Greiner,et al.  Principles and practical application of the receiver-operating characteristic analysis for diagnostic tests. , 2000, Preventive veterinary medicine.

[34]  M Schemper,et al.  A note on quantifying follow-up in studies of failure time. , 1996, Controlled clinical trials.

[35]  K R Hess,et al.  Graphical methods for assessing violations of the proportional hazards assumption in Cox regression. , 1995, Statistics in medicine.

[36]  F. Harrell,et al.  Regression modelling strategies for improved prognostic prediction. , 1984, Statistics in medicine.

[37]  J. Hanley,et al.  The meaning and use of the area under a receiver operating characteristic (ROC) curve. , 1982, Radiology.

[38]  M Schumacher,et al.  A bootstrap resampling procedure for model building: application to the Cox regression model. , 1992, Statistics in medicine.

[39]  J J Shuster,et al.  Median follow-up in clinical trials. , 1991, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.